The major overall aim of this Program Project is to develop strategies for restoring sensorimotor function after spinal cord injury. These strategies include transplants of genetically modified cells, and pharmacological manipulations. Even if such strategies are successful in restoring connections across a spinal cord injury, the brain may not be able to control the spinal cord circuits because of the well known tendency of the CNS to "remap" after peripheral injuries. Thus, the major aim of this project is to investigate changes in the neurophysiological organization of the supraspinal sensorimotor systems after spinal cord injury, including hemisection and transection, and after transplants and pharmacological intervention. All experiments will utilize our techniques for chronically stimulating and/or recording from large populations of neurons through electrode arrays implanted in several regions of the brain. These techniques are well suited to the problem of measuring functional changes in neuronal ensembles over both short and long time periods (i.e. from seconds to months) and over difficult experimental manipulations (e.g. spinal cord injury). These electrode implants will be used to assess time-dependent changes in 1- neuronal discharge properties, 2- somatosensory maps, 3- motor maps, defined by microstimulation through the same electrodes to directly evoke peripheral movements, and 4- "motor correlates" of neurons recorded during movement. Experiment induced changes in these parameters will be assessed by recording through electrode arrays chronically implanted bilaterally in the sensorimotor cortex (SMC) and red nucleus (RN) in rats. Such data will be routinely obtained from the same animals over all of the experimental manipulations described below (Aim 1: adult hemisection; Aim 2: neonatal spinal rats; Aim 3: adult spinal rats). Three questions will be addressed: 1- Do supraspinal sensorimotor system (e.g. SMC and RN) neurons exhibit a predictable time course of functional change after spinal cord injury?, 2- To what extent can these changes be prevented or reversed by transplanting genetically modified cells into the injury site, in neonates or adults?, and 3- to what extent can these changes be modified by training, such as the direct conditioning of SMC neuronal activity that we have recently demonstrated (Chapin et al., 99)?